Dendritic and Axonal Architecture of Individual Pyramidal Neurons across Layers of Adult Human Neocortex

Abstract

The size and shape of dendrites and axons are strong determinants of neuronal information processing. Our knowledge on neuronal structure and function is primarily based on brains of laboratory animals. Whether it translates to human is not known since quantitative data on “full” human neuronal morphologies are lacking. Here, we obtained human brain tissue during resection surgery and reconstructed basal and apical dendrites and axons of individual neurons across all cortical layers in temporal cortex (Brodmann area 21). Importantly, morphologies did not correlate to etiology, disease severity, or disease duration. Next, we show that human L(ayer) 2 and L3 pyramidal neurons have 3-fold larger dendritic length and increased branch complexity with longer segments compared with temporal cortex neurons from macaque and mouse. Unsupervised cluster analysis classified 88% of human L2 and L3 neurons into human-specific clusters distinct from mouse and macaque neurons. Computational modeling of passive electrical properties to assess the functional impact of large dendrites indicates stronger signal attenuation of electrical inputs compared with mouse. We thus provide a quantitative analysis of “full” human neuron morphologies and present direct evidence that human neurons are not “scaled-up” versions of rodent or macaque neurons, but have unique structural and functional properties.

Unique membrane properties and enhanced signal processing in human neocortical neurons

“…Starting with the seminal work of Santiago Ramón y Cajal (Cajal, 1995) and Camilo Golgi (Golgi, 1906), and continuing with modern anatomical studies (Jacobs et al, 2001; Watson et al, 2006; DeFelipe, 2011), anatomists have been fascinated by its cellular structure. Comparison of human and rodents cortices shows that the human cortex is thicker (in particular layer 2/3 [DeFelipe et al, 2002; Elston et al, 2001]), contains more white matter (Herculano-Houzel et al, 2010), its neurons are larger (Mohan et al, 2015), and its cortical pyramidal cells have more synaptic connections per cell (15,000–30,000 for layer 2/3 pyramidal neurons [DeFelipe, 2011; DeFelipe et al, 2002]). It seems that the human neocortex, and especially its neurons, is anatomically unique.…”

“…To collect this data, fresh cortical tissue was obtained from brain operations at the neurosurgical department in Amsterdam. Details can be found in our previous works (Testa-Silva et al, 2010; Verhoog et al, 2013; Testa-Silva et al, 2014; Mohan et al, 2015), as well as in the work of other groups (Schwartzkroin and Prince, 1978; Szabadics et al, 2006; Köhling and Avoli, 2006). Our models of human neurons also incorporate data on dendritic spines obtained from light-microscope studies in HL2/3 PCs (Benavides-Piccione et al, 2013; DeFelipe et al, 2002; Elston et al, 2001).…”

Connectomic Analysis of Brain Networks: Novel Techniques and Future Directions

“…This method has allowed the production of detailed catalogs of virtually all the neuron types in localized regions of juvenile cerebral cortex or hippocampus, based on both their somatodendritic and local axon morphologies and their membrane properties (Li et al, 1994; DeFelipe et al, 2013; Markram et al, 2015). This technique, however, is not ideal for use on adult brain tissue, as adult cells are more vulnerable to damage by the sectioning procedure (Huang and Uusisaari, 2013; see however Mohan et al, 2015, on adult human biopsic samples). In any case, however, labeling in slices is unsuitable to study the vast axonal trees of long-range projection neurons, as they usually extend far beyond the dimensions of any viable slice preparation (Kuramoto et al, 2009; Economo et al, 2016).…”

Whole cell patch clamp analysis of non-synaptic and synaptic signaling in rodent and human supragranular neocortex

“…In the past decade, increasing attention has been put on special features of the human neocortex microcircuits comparing them to those of other mammals such as non-human primates, carnivores, and rodents (Boldog et al, 2017;Komlósi et al, 2012;Mohan et al, 2015;Molnár et al, 2008;Oláh et al, 2007;Prince and Wong, 1981;Schwartzkroin and Knowles, 1984;Verhoog et al, 2013;Wang et al, 2015;Yáñez et al, 2005). Species-specific differences evidently exist in various anatomical features of the neocortex including the layering, some long-range connections and some intrinsic electrical and morphological properties of nerve cells (Boldog et al, 2017;Mohan et al, 2015;Wang et al, 2015).…”

“…Species-specific differences evidently exist in various anatomical features of the neocortex including the layering, some long-range connections and some intrinsic electrical and morphological properties of nerve cells (Boldog et al, 2017;Mohan et al, 2015;Wang et al, 2015). Yet,it has been thought that basic cellular elements and local synaptic circuits are fairly stereotyped among mammalian species and largely similar for instance between a rodent and a human.…”